Mechanisms for central regulation of the substrates of cellular energy metabolism (free fatty acids and glucose) will be investigated in primates. The operational characteristics of substrate regulating systems will be studied in fasted baboons and then compared in experimental diabetes and obesity. In these studies, emphasis will be placed upon disrupting the equilibrium of fasting with small physiologic stimuli, thereby hopefully avoiding mobilization of secondary compensatory mechanisms. T3resholds for inducing changes in plasma free fatty acids or glucose by various substances will be determined. A search will be made for substances related to adipose tissue metabolsim which might act as stimuli to substrate regulation. Direct evidence will be sought for central nervous system participation in substrate regulation under various physiologic conditions. These studies will be done in the baboon prepared for intracarotid infusion in the unanesthetized state. With this preparation, specific hypothalamic centers will be ablated or stimulated through stereotactically implanted electrodes. The effector pathways of central substrate regulation will be studied with the goal of defining the quantitative role of the autonomic nervous system and the neuroendocrine system in a variety of physiological and pathological states. With better definition of normal regulatory mechanisms, abnormalities in diabetes and obesity may be more accurately defined.